Show simple item record

dc.contributor.authorNath Artika P
dc.contributor.authorRitchie Scott C
dc.contributor.authorByars Sean G
dc.contributor.authorFearnley Liam G
dc.contributor.authorHavulinna Aki S
dc.contributor.authorJoensuu Anni
dc.contributor.authorKangas Antti J
dc.contributor.authorSoininen Pasi
dc.contributor.authorWennerström Annika
dc.contributor.authorMilani Lili
dc.contributor.authorMetspalu Andres
dc.contributor.authorMännistö Satu
dc.contributor.authorWürtz Peter
dc.contributor.authorKettunen Johannes
dc.contributor.authorRaitoharju Emma
dc.contributor.authorKähönen Mika
dc.contributor.authorJuonala Markus
dc.contributor.authorPalotie Aarno
dc.contributor.authorAla-Korpela Mika
dc.contributor.authorRipatti Samuli et al.
dc.date.accessioned2017-12-18T13:11:23Z
dc.date.available2017-12-18T13:11:23Z
dc.date.issued2017
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/5100
dc.description.abstractBackground Immunometabolism plays a central role in many cardiometabolic diseases. However, a robust map of immune-related gene networks in circulating human cells, their interactions with metabolites, and their genetic control is still lacking. Here, we integrate blood transcriptomic, metabolomic, and genomic profiles from two population-based cohorts (total N = 2168), including a subset of individuals with matched multi-omic data at 7-year follow-up. Results We identify topologically replicable gene networks enriched for diverse immune functions including cytotoxicity, viral response, B cell, platelet, neutrophil, and mast cell/basophil activity. These immune gene modules show complex patterns of association with 158 circulating metabolites, including lipoprotein subclasses, lipids, fatty acids, amino acids, small molecules, and CRP. Genome-wide scans for module expression quantitative trait loci (mQTLs) reveal five modules with mQTLs that have both cis and trans effects. The strongest mQTL is in ARHGEF3 (rs1354034) and affects a module enriched for platelet function, independent of platelet counts. Modules of mast cell/basophil and neutrophil function show temporally stable metabolite associations over 7-year follow-up, providing evidence that these modules and their constituent gene products may play central roles in metabolic inflammation. Furthermore, the strongest mQTL in ARHGEF3 also displays clear temporal stability, supporting widespread trans effects at this locus. Conclusions This study provides a detailed map of natural variation at the blood immunometabolic interface and its genetic basis, and may facilitate subsequent studies to explain inter-individual variation in cardiometabolic disease.en
dc.language.isoENen
dc.publisherSpringer Natureen
dc.relation.ispartofseriesGENOME BIOLOGY [ONLINE]en
dc.relation.urihttp://dx.doi.org/10.1186/s13059-017-1279-yen
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/en
dc.titleAn interaction map of circulating metabolites, immune gene networks, and their genetic regulationen
dc.description.versionpublished versionen
dc.contributor.departmentSchool of Pharmacy, Activitiesen
uef.solecris.id49139910en
dc.type.publicationinfo:eu-repo/semantics/articleen
dc.rights.accessrights© Authorsen
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/FP7-INFRASTRUCTURES/313010/EU/BBMRI - Large Prospective Cohorts/BBMRI-LPCen
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/FP7-HEALTH /305280/EU/ Methods for Integrated analysis of Multiple Omics datasets/MIMOmics
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/H2020-EU.3.1.1. - Understanding health, wellbeing and disease/633589/EU/Validating C. elegans healthspan model for better understanding factors causing health and disease, to develop evidence based prevention, diagnostic, therapeutic and other strategies/Ageing with elegans
dc.relation.doi10.1186/s13059-017-1279-yen
dc.description.reviewstatuspeerRevieweden
dc.relation.articlenumber146en
dc.relation.issn1474-760Xen
dc.relation.volume18en
dc.rights.accesslevelopenAccessen
dc.type.okmA1en
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
uef.solecris.openaccessOpen access -julkaisukanavassa ilmestynyt julkaisu


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record